Longitudinal Study of Insulin Resistance and Sex Hormones over the Menstrual Cycle: The BioCycle Study

摘要

Context: Conflicting findings have been reported regarding the effect of menstrual cycle phase and sex hormones on insulin sensitivity.Objective: The aim was to determine the pattern of insulin resistance over the menstrual cycle and whether variations in sex hormones explain these patterns.Design: The BioCycle study is a longitudinal study that measured hormones at different phases of the menstrual cycle. Participants had up to eight visits per cycle; each visit was timed using fertility monitors to capture sensitive windows of hormonal changes.Setting: The study was conducted in the general community of the University at Buffalo (Buffalo, NY).Participants: A total of 257 healthy, premenopausal women (age, 27 ± 8 yr; body mass index, 24 ± 4 kg/m~(2)) participated in the study.Main Outcome Measures: We measured fasting insulin, glucose, and insulin resistance by the homeostasis model of insulin resistance (HOMA-IR).Results: Significant changes in HOMA-IR were observed over the menstrual cycle; from a midfollicular phase level of 1.35, levels rose to 1.59 during the early luteal phase and decreased to 1.55 in the late-luteal phase. HOMA-IR levels primarily reflected changes in insulin and not glucose. After adjustment for age, race, cycle, and other sex hormones, HOMA-IR was positively associated with estradiol (β = 0.082; P < 0.001) and progesterone (β = 0.025; P < 0.001), and inversely associated with FSH (adjusted β = ?0.040; P < 0.001) and SHBG (β = ?0.085; P < 0.001). LH was not associated with HOMA-IR. Further adjustment for BMI weakened the association with SHBG (β = ?0.057; P = 0.06) but did not affect other associations.Conclusion: Insulin exhibited minor menstrual cycle variability. Estradiol and progesterone were positively associated with insulin resistance and should be considered in studies of insulin resistance among premenopausal women.